Constituents from the Polar Extract of Pisolithus arhizus and Their Anti-inflammatory Activity.

The phytochemical study of the Pisolithus arhizus fruiting body methanol extract led to the isolation of six new triterpenoids (1-6) and one new naphthalenoid pulvinic acid derivative (7), together with five known compounds, including norbadione A (8). Their structure was established from 1D and 2D NMR spectroscopy and HRESIMS analyses. The absolute configuration of the triterpenoids was determined by circular dichroism. The two pulvinic acid derivatives 7 and 8, showing the highest activity in modulating IL-6 secretion, were tested for their effect on COX-2, STAT3, and p-STAT3 proteins; both compounds were able to downregulate p-STAT3.

Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance.

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1ß which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.

Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue: a systematic review and meta-analysis.

BACKGROUND: Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. METHODS: A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses. RESULTS: All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively). CONCLUSIONS: Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.

Specialized metabolites from plants as a source of new multi-target antiviral drugs: a systematic review.

Viral infections have always been the main global health challenge, as several potentially lethal viruses, including the hepatitis virus, herpes virus, and influenza virus, have affected human health for decades. Unfortunately, most licensed antiviral drugs are characterized by many adverse reactions and, in the long-term therapy, also develop viral resistance; for these reasons, researchers have focused their attention on investigating potential antiviral molecules from plants. Natural resources indeed offer a variety of specialized therapeutic metabolites that have been demonstrated to inhibit viral entry into the host cells and replication through the regulation of viral absorption, cell receptor binding, and competition for the activation of intracellular signaling pathways. Many active phytochemicals, including flavonoids, lignans, terpenoids, coumarins, saponins, alkaloids, etc., have been identified as potential candidates for preventing and treating viral infections. Using a systematic approach, this review summarises the knowledge obtained to date on the in vivo antiviral activity of specialized metabolites extracted from plant matrices by focusing on their mechanism of action.

Oral Anticoagulation for Atrial Fibrillation in Octogenarians Across the Renal Function Spectrum.

PURPOSE: Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in octogenarians with atrial fibrillation (AF) across the spectrum of renal function. METHODS: Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized in 2 groups according to creatinine clearance (CrCl) ≥ 45 and < 45 ml/min/1.73 m2. The primary safety outcome was the occurrence major bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events. RESULTS: A total of 901 AF patients (median age 84 [4.9] years; 44% men) with age ≥ 80 years on treatment with DOACs (n: 629, 70%) and VKA (n: 272, 30%) were included in the study. 303 patients (34%) had CrCl < 45 ml/min/1.73m2 and 598 (66%) had CrCl ≥ 45 ml/min/1.73m2. No significant differences were shown in major bleedings, minor bleedings and thromboembolic events between patients on DOACs vs VKAs, both in the group with CrCl ≥ 45 than < 45 ml/min. In the group with CrCl < 45 ml/min/1.73 m2, a total of 72 patients (23%) died during the follow-up, with higher mortality in VKA group compared to DOACs (45% vs 15%; p < 0.001). At multivariate regression analysis, age [OR: 1.15; p = 0.001] and coronary artery disease (CAD) [OR: 1.74; p = 0.04] were independently associated with mortality; in contrast, the use of DOACs were inversely associated with mortality [OR = 0.26; p < 0.001]. In patients with CrCl ≥ 45 ml/min/1.73 m2, DOACs group experienced less intra-cranial hemorrhage (ICH) (0.2% vs 2.8%; p = 0.01) compared to VKAs. VKAs patients showed higher mortality compared to those on DOACs (29.1% vs 7.9%; p < 0.001). At multivariate regression analysis, chronic heart failure [OR = 2.14; p = 0.01] was independently associated with death, whereas male gender [OR: 0.45; p = 0.009] and the use of DOACs [OR: 0.29; p < 0.001] were associated with lower mortality. CONCLUSION: DOACs seem to be safe and effective in octogenarians with chronic kidney disease at stage ≥ G3b. As compared with VKA administration, the use of DOACs was associated with lower mortality rates among AF octogenarians with renal dysfunction.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

Clinical impact of oral anticoagulation among octogenarians with atrial fibrillation and anaemia.

Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in elderly patients (> or = 80 years-old) with atrial fibrillation (AF) and concomitant anaemia. Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized as anaemic and non-anaemic. The primary outcome was the occurrence of overall bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events (a composite of ischemic stroke, transient ischemic attack and systemic embolism). The secondary safety and effectiveness outcomes were major, minor bleedings and mortality, respectively. A total of 958 patients were included in the study, 120 (12.5%) were anaemic; among them, 93 patients (76.6%) were treated with VKAs and 28 (23.3%) with DOAC. Kaplan-Meier curves for major bleedings showed significant differences between anemic- and non-anemic groups (log-rank p = 0.005). In multivariate analysis, among patients on OAC, anaemia was independently associated with major bleeding (HR 2.36; 95% IC 1.2-4.4; p = 0.006), intracranial hemorrhages (HR 3.81; 95% IC 1.35-10.7; p = 0.01) and minor bleedings (HR 2.40; 95%IC 1.1-5.2; p = 0.02); these associations were not confirmed in the DOACs subgroup. No difference in survival was shown between anaemic- and non-anaemic groups and among anaemic patients, between DOAC and VKAs subgroups. Anaemic octogenarians with AF on OAC therapy showed a significantly increased risk of major bleedings, in particular ICH, and mortality compared to non-anaemic.

The prognostic role of interatrial block among COVID-19 patients hospitalized in medicine wards.

INTRODUCTION: Some abnormal electrocardiographic findings were independently associated with increased mortality in patients admitted for COVID-19; however, no studies have focussed on the prognosis impact of the interatrial block (IAB) in this clinical setting. The aim of our study was to assess the prevalence and clinical implications of IAB, both partial and advanced, in hospitalized COVID-19 patients. MATERIALS: We retrospectively evaluated 300 consecutive COVID-19 patients (63.22 ± 15.16 years; 70% males) admitted to eight Italian Hospitals from February 2020 to April 2020 who underwent twelve lead electrocardiographic recording at admission. The study population has been dichotomized into two groups according to the evidence of IAB at admission, both partial and advanced. The differences in terms of ARDS in need of intubation, in-hospital mortality and thromboembolic events (a composite of myocardial infarction, stroke and transient ischaemic attack) have been evaluated. RESULTS: The presence of IAB was noticed in 64 patients (21%). In the adjusted logistic regression model, the partial interatrial block was found to be an independent predictor of ARDS in need of intubation (HR: 1.92; p: .04) and in-hospital mortality (HR: 2.65; p: .02); moreover, the advanced interatrial block was an independent predictor of thrombotic events (HR: 7.14; p < .001). CONCLUSIONS: Among COVID-19 patients hospitalized in medical wards, the presence of interatrial block is more frequent than in the general population and it might be useful as an early predictor for increased risk of incident thrombotic events, ARDS in need of intubation and in-hospital mortality.

Prevalence and clinical predictors of inappropriate direct oral anticoagulant dosage in octagenarians with atrial fibrillation.

PURPOSE: Older age is associated with inappropriate dose prescription of direct oral anticoagulants. The aim of our study was to describe the prevalence and the clinical predictors of inappropriate DOACs dosage among octogenarians in real-world setting. METHODS: Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation (AF) Research Database (NCT03760874). Of the AF patients aged ≥ 80 who received DOACs treatment, 253 patients were selected. Participants were categorized as appropriate dosage, overdosage, or underdosage. Underdosage and overdosage were, respectively, defined as administration of a lower or higher DOAC dose than recommended in the EHRA consensus. RESULTS: A total of 178 patients (71%) received appropriate DOACs dose and 75 patients (29%) inappropriate DOACs dose; among them, 19 patients (25.6%) were overdosed and 56 (74.4%) were underdosed. Subgroup analysis demonstrated that underdosage was independently associated with male gender [OR = 3.15 (95% IC; 1.45-6.83); p < 0.001], coronary artery disease [OR = 3.60 (95% IC 1.45-9.10); p < 0.001] and body mass index [OR = 1.27 (1.14-1.41); p < 0.001]. Overdosage was independently associated with diabetes mellitus [OR = 18 (3.36-96); p < 0.001], with age [OR = 0.76 (95% IC; 0.61-0.96; p = 0.045], BMI [OR = 0.77 (95% IC; 0.62-0.97; p = 0.043] and with previous bleedings [OR = 6.40 (0.7; 1.43-28); p = 0.039]. There wasn't significant difference in thromboembolic, major bleeding events and mortality among different subgroups. Underdosage group showed a significatively lower survival compared with appropriate dose group (p < 0.001). CONCLUSION: In our analysis, nearly one-third of octogenarians with AF received an inappropriate dose of DOAC. Several clinical factors were associated with DOACs' overdosage (diabetes mellitus type II, previous bleeding) or underdosage (male gender, coronary artery disease, and higher body mass index). Octogenarians with inappropriate DOACs underdosage showed less survival.

Diterpenoid Constituents of Psiadia punctulata and Evaluation of Their Antimicrobial Activity.

Sixteen diterpenes (1-16), along with 10 previously described compounds, including four flavonoids and six diterpenes, were isolated from the aerial parts of Psiadia punctulata growing in Saudi Arabia. The diterpene structures were elucidated using NMR spectroscopy and mass spectrometry data. Furthermore, a DFT/NMR procedure was used to suggest the relative configuration of several compounds. The labdane-derived skeletons, namely, ent-atisane, ent-beyerene, ent-trachylobane, and ent-kaurene, were identified. The extracts, fractions, and pure compounds were then tested against Staphylococcus aureus, Streptococcus mutans, Treponema denticola, and Lactobacillus plantarum. One diterpenoid, namely, psiadin, showed an additive effect with the antiseptic chlorhexidine, with a fractional inhibitory concentration index of less than 1. Additionally, psiadin showed a prospective inhibition activity for bacterial efflux pumps.

Cytotoxic Sesquiterpenoids from Ammoides atlantica Aerial Parts.

Seven new terpenoids, namely, guaiane (1-4), eudesmane (5), and bisabolane (6) sesquiterpenoids and a furanone (7), were isolated from the aerial parts of Ammoides atlantica, a herbaceous plant growing in Algeria, together with eight known compounds. All metabolites were characterized by their 1D and 2D NMR and HRESIMS data. A combined DFT/NMR method was applied to study the relative configurations of 1-4, 6, and 7. All compounds, except 2, were assayed against MCF-7, A375, A549, HaCaT, and Jurkat cell lines. Compounds 8, 10, and 11 induced a dose-dependent reduction in cell viability with different potency on almost all cell lines used. The most active compounds, 8 and 10, were studied to assess their potential apoptotic effects and cell cycle inhibition.

Positive predictive values and outcomes for uninformative cell-free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study).

OBJECTIVES: To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories. METHODS: Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed. RESULTS: Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow-up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound. CONCLUSIONS: NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre- and post-test counselling.

Incidental finding of rare and huge asymptomatic pseudoaneurysm after Bentall procedure: A challenging case report.

We report the case of a 62-year-old male who underwent urgent cardiac surgery due to the incidental finding of a huge and asymptomatic coronary button pseudoaneurysm at an 18-month outpatients clinic follow-up requiring a very complex preoperative planning.

Renal function and cardiac adrenergic impairment in patients affected by heart failure.

Although in heart failure (HF) there is a strict correlation between heart and kidney, no data are available on the potential relationship in HF between renal dysfunction (RD) and the impaired sympathetic innervation. Aim of the present study was to assess the relationship between RD and cardiac sympathetic innervation in HF patients with reduced ejection fraction. Two hundred and sixty-three patients with mild-to-severe HF underwent iodine-123 meta-iodobenzylguanidine myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart-to-mediastinum (H/M) ratios and washout rate. In all patients, glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was assessed. A direct association was found between EPI-eGFR and late H/M (r = .215; P < .001). Dividing the population into moderate-to-severe eGFR reduction and normal-to-mildly reduced eGFR (cutoff ≤ 60 mL·min-1·1.73 m-2), a statistically significant reduction of late H/M value was found in patients with RD compared to patients with preserved eGFR (P = .030). By multivariable linear regression analysis, eGFR resulted in the prediction of impaired late H/M in patients with RD (P = .005). Patients with RD and HF show more impaired cardiac sympathetic activity than HF patients with preserved renal function, and reduced eGFR is a predictor of reduced late H/M.

Direct Current Cardioversion in Atrial Fibrillation Patients on Edoxaban Therapy Versus Vitamin K Antagonists: a Real-world Propensity Score-Matched Study.

PURPOSE: The purpose of the present study was to compare the long-term effectiveness and safety of newly initiated anticoagulation with edoxaban (EDO) versus uninterrupted vitamin K antagonist (VKA) therapy in patients with atrial fibrillation (AF) scheduled for transesophageal echocardiogram (TEE)-guided direct electrical current cardioversion (DCC). METHODS: A propensity score-matched cohort observational study was performed comparing the safety and effectiveness of edoxaban versus well-controlled VKA therapy among a cohort of consecutive non-valvular AF patients scheduled for DCC. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). FINDINGS: A total of 130 AF patients receiving edoxaban 60-mg (EDO) treatment were compared with the same number of VKA recipients. The cumulative incidence of major bleedings was 1.54% in the EDO group and 3.08% in the VKA group (P = 0.4). The cumulative incidence of thromboembolic events was 1.54% in the EDO group and 2.31% in the VKA group (P = 0.9). A non-significant trend in improved adherence was observed between the EDO and VKA groups with a total anticoagulant therapy discontinuation rate of 4.62% (6/130) vs 6.15% (8/130), respectively (P = 0.06). IMPLICATIONS: Our study provides the evidence of a safe and effective use of edoxaban in this clinical setting, justified by no significant difference in major bleedings and thromboembolic events between edoxaban and well-controlled VKA treatments.

Nor-abietane Diterpenoids from Perovskia abrotanoides Roots with Anti-inflammatory Potential.

Fractionation of an EtOAc extract of the roots of Perovskia abrotanoides yielded 28 diterpenoids, including 12 new analogues, 1-12. The structures of these diterpenoids were established using comprehensive spectroscopic data analysis, including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism spectroscopy, and comparison with literature data. The extract and some of the tested compounds showed significant anti-inflammatory activity on J774A.1 macrophage cells stimulated with E. coli lipopolysaccharide. In particular, the tested compounds significantly inhibited the release of nitric oxide and the expression of related proinflammatory enzymes, such as inducible nitric oxide synthase.

The role of inflammation and metabolic risk factors in the pathogenesis of calcific aortic valve stenosis.

Given the epidemiologic increase of aged population in the world, aortic stenosis (AS) represents now the most common valvular heart disease in industrialized countries. It is a very challenging disease, representing an important cause of morbidity, hospitalization and death in the elderly population. It is widely recognized that AS is the result of a very complex active process, driven by inflammation and involving multifactorial pathological mechanisms promoting valvular calcification and valvular bone deposition. Several evidence suggest that epicardial adipose tissue (EAT), the visceral fat depot of the heart, represents a direct source of cytokines and could mediate the deleterious effects of systemic inflammation on the myocardium. Importantly, obesity and metabolic disorders are associated with chronic systemic inflammation leading to a significant increase of EAT amount and to a pro-inflammatory phenotypic shift of this fat depot. It has been hypothesized that the EAT inflammatory state can influence the structure and function of the heart, thus contributing to the pathogenesis of several cardiac diseases, including calcific AS. The current review will discuss the recently discovered mechanisms involved in the pathogenesis of AS, with particular attention to the role of inflammation, metabolic risk factors and pro-fibrotic and pro-osteogenic signal pathways promoting the onset and progression of the disease. Moreover, it will be explored the potential role of EAT in the AS pathophysiology.

Non-vitamin K vs vitamin K oral anticoagulants in patients aged > 80 year with atrial fibrillation and low body weight.

BACKGROUND: Octogenarian patients are at high risk of both ischaemic and bleeding events, and the low body weight is considered a risk factor for major bleeding in atrial fibrillation (AF) patients on anticoagulation therapy. The aim of our study was to compare the safety and effectiveness of NOACs versus well-controlled VKA therapy among patients aged > 80 year with AF and low body weight in real-life setting. METHODS: Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation Research Database (NCT03760874). From this, we selected AF patients aged ≥ 80 years and weighted ≤ 60 kg who received NOACs or VKAs treatment (only those with a time in therapeutic range > 70%). 279 patients (136 in NOAC group and 143 in VKA group) were selected. RESULTS: A total of 71 patients (17 in NOAC vs 54 in VKA group) died during the follow-up. The incidence rate of all-cause mortality was 27.70 per 100 person-years (14.91 in NOAC vs 37.94 in VKA group, adjusted hazard ratio 0.43; 95% CI 0.25 to 0.975; P = .003). 22 patients (9 in NOAC vs 13 in VKA group, P = .6) had major bleeding events. Diabetes mellitus, COPD and age resulted positively associated with death, whereas NOACs, parossistic AF and weight negatively associated with mortality. CONCLUSIONS: Our real-world data might suggest the safe and efficacy use of NOACs in this setting of population, justified by a reduction in overall mortality over VKAs. Further studies are needed to confirm these data.

Validation of the echocardiographic assessment of epicardial adipose tissue thickness at the Rindfleisch fold for the prediction of coronary artery disease.

BACKGROUND AND AIM: Echocardiography is a promising technique for the assessment of epicardial adipose tissue (EAT). Increased EAT thickness is associated with different cardiac diseases, including; coronary artery disease (CAD). Since several different echocardiographic approaches have been proposed to measure EAT, the identification of a standardized method is needed. We propose the assessment of EAT maximal thickness at the Rindfleisch fold, the reproducibility of this measurement and its correlation with EAT thickness and volume assessed at cardiac magnetic resonance (CMR). Finally, we will test the predictive role of this measurement on the presence of significant CAD. METHODS AND RESULTS: In 1061 patients undergoing echocardiography, EAT thickness was measured at the level of the Rindfleisch fold. In 70 patients, we tested the relationship between echo-EAT thickness and EAT thickness and volume assessed at CMR. In 499 patients with suspected CAD, undergoing coronary artery angiography, we tested the predictive value of EAT on the presence of significant CAD. Echo-EAT thickness measurements had an excellent reliability as indicated by the inter-observer (ICC:0.97; 95% C.I. 0.96 to 0.98) and intra-observer (ICC:0.99; 95% C.I. 0.98 to 0.99) reliability rates. Echo-EAT thickness significantly correlated with CMR-EAT thickness and volume (p < 0.001). An EAT thickness value >10 mm discriminated patients with significant CAD at coronary angiography (p < 0.001). At multivariable analysis, including demographic data and cardiovascular risk factors, EAT thickness was an independent predictor of significant CAD and showed an additive predictive value over common atherosclerotic risk factors. CONCLUSIONS: Echocardiographic assessment of EAT thickness at the level of the Rindfleisch fold represents a simple and trustworthy method. An increased EAT thickness shows an additive predictive value on CAD over common atherosclerotic risk factors, thus suggesting its potential clinical use for CAD risk stratification.

Clinical profile of direct oral anticoagulants versus vitamin K anticoagulants in octogenarians with atrial fibrillation: a multicentre propensity score matched real-world cohort study.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its prevalence increases with age. Few data are available about the clinical performance of direct oral anticoagulant (DOACs) in patients aged ≥ 80 years with AF. The aim of our propensity score matched cohort study was to compare the safety and efficacy of DOACs versus well-controlled VKA therapy among octogenarians with AF in real life setting. Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation Research Database (NCT03760874), which includes all AF patients followed by the participating centers, through outpatient visits every 3 to 6 months. The database was queried for AF patients aged ≥ 80 years who received DOACs or VKAs treatment. The primary effectiveness endpoint was the occurrence of thromboembolic events (a composite of stroke, transient ischemic attack, systemic embolism); the primary safety endpoint was the occurrence of major bleeding; the secondary endpoint was all-cause mortality. The database query identified 774 AF patients aged ≥ 80 years treated with VKAs and 279 with DOACs. Propensity score (2:1) matching selected 252 DOAC and 504 VKA recipients. The mean follow-up was 31.07 ± 14.09 months. The incidence rate of thromboembolic events was 13.79 per 1000 person-years [14.80 in DOAC vs 13.34 in VKA group, Hazard Ratio 1.10; 95% confidence interval (CI) 0.49 to 2.45; P = 0.823]. The incidence rate of intracranial hemorrhage (ICH) was 8.06 per 1000 person-years (3.25 in DOAC vs 10.23 in VKA group, HR 0.33; 95% CI 0.07 to 1.45; P = 0.600). Through these incidence rates, we found a positive net clinical benefit (NCB) of DOACs over VKAs, equal to + 9.01. The incidence rate of all-cause mortality was 105.05 per 1000 person-years (74.67 in DOAC vs 118.67 in VKA group, Hazard Ratio 0.65; 95% CI 0.47 to 0.90; P = 0.010). The concomitant use of antiinflammatory drugs (HR 7.90; P < 0.001) were found to be independent predictor of major bleeding. Moreover, age (HR 1.17; P < 0.002) and chronic kidney disease (HR 0.34; P = 0.019) were found to be independently associated with thromboembolic events. In our study no significant difference in terms of both thromboembolic and major bleeding events, but a significant lower incidence of all-cause mortality, was detected in AF patients aged ≥ 80 years treated with DOACs vs VKAs.